益气养阴活血方对糖尿病肾病大鼠NFAT2/COX-2的影响

目的:探讨益气养阴活血方对糖尿病肾病(DN)大鼠肾脏保护作用及其机制。方法:50只雄性SD大鼠随机分为正常组8只、造模组42只。除正常组外,造模组腹腔注射链脲佐菌素(STZ)诱导建立DN大鼠模型,造模成功的32只DN大鼠随机分为模型组、缬沙坦组、益气养阴活血方低剂量组及益气养阴活血方高剂量组,每组8只。灌胃6周后全自动生化分析仪检测各组大鼠血肌酐(Scr)、尿素氮(BUN)、空腹血糖(FBG)、24 h尿蛋白总量(24 h-UTP);Western blot及荧光定量PCR分别检测肾脏NFAT2、COX-2相关蛋白及其mRNA表达;苏木素-伊红(HE)染色观察大鼠肾脏病理变化。结果:与正常组比较,模型组大鼠肾小球、肾小管病理损伤较重,血清Scr、BUN、FBG、24 h-UTP、肾组织NFAT2、COX-2相关蛋白及其mRNA表达水平均升高(P＜0.01);与模型组比较,益气养阴活血方干预组大鼠肾脏病理明显改善,血清Scr、BUN、FBG、24 h-UTP、肾组织NFAT2、COX-2相关蛋白及其mRNA表达水平均降低(P＜0.01,P＜0.05)。结论:益气养阴活血方可能通过下调NFAT2/COX-2信号通路而减轻肾脏病理损害,保护肾功能,降低尿蛋白。

Effect of Yiqi Yangyin Huoxue Recipe on NFAT2/COX-2 in diabetic nephropathy rats

OBJECTIVE To explore the renal protective effect and mechanism of Yiqi Yangyin Huoxue Recipe in diabetic nephropathy (DN) rats.METHODS Totally 50 male SD rats were randomly divided into normal group (n=8) and model group (n=42). The model of DN was established by intraperitoneal injection of streptozotocin (STZ). Totally 32 DN rats were randomly divided into model group, valsartan group, Yiqi Yangyin Huoxue Recipe low-dose group and Yiqi Yangyin Huoxue Recipe high-dose group with 8 rats in each group. After 6 weeks of gavage, the automatic biochemical analyzer was used to detect serum creatinine (Scr), blood urea nitrogen (BUN), fasting blood glucose (FBG), and 24-hours urine protein (24h-UTP); Western blot and fluorescence quantitative PCR were used to detect the expression of NFAT2 and COX-2-related proteins and their mRNA in kidney. Hematoxylin-eosin (HE) staining was used to observe the pathological changes of kidney tissue.RESULTS Compared with that in the normal group, the pathological damage of the glomerulus and renal tubules in the model group was more severe, and the expression levels of Scr, BUN, FBG, 24h-UTP, NFAT2, COX-2-related proteins and their mRNA in renal tissue were increased (P＜0.01). Compared with that in the model group, the pathological damage of the kidney tissue lesions in the intervention groups of Yiqi Yangyin Huoxue Recipe were significantly improved, and the expression levels of Scr, BUN, FBG, 24h-UTP, NFAT2, COX-2-related proteins and their mRNA in renal tissue were decreased (P＜0.01, P＜0.05).CONCLUSION Yiqi Yangyin Huoxue Recipe may reduce renal pathological damage, protect renal function and reduce urinary protein by down-regulating NFAT2/COX-2 signal pathway.